Distinct role of follicular dendritic cells and T cells in the proliferation, differentiation, and apoptosis of a centroblast cell line, L3055

Germinal center (GC) B cells undergo complex interactions with follicular d endritic cells (FDC) and T cells in the course of differentiation into memo ry B and plasma cells. To delineate the individual roles of FDC and T cells at each stage of GC B cell differentiation at the clonal level and to anal yze the signals involved, we adopted a unique experimental model using an F DC line, HK, and a lymphoma cell line, L3055, that resembles centroblasts, A detailed phenotypic analysis revealed L3055 cells to be a clonal populati on originating from the GC, Like freshly isolated centroblasts, L3055 cells underwent spontaneous apoptosis when cultured in the absence of fresh FDC or HK cells. L3055 cells proliferated continuously in the presence of Hg ce lls, while they differentiated into a population with the phenotype of cent rocytes after stimulation with CD40 ligand (CD40L) and IL-4. The CD40L-stim ulated L3055 cells underwent CD95-mediated apoptosis, which was reminiscent of the feature of CD40L-stimulated tonsillar GC B cells. In contrast to HK cells that did not protect L3055 cells from anti-Ig killing, CD40L plus IL -2, IL-4, and IL-10 prevented anti-Ig-induced apoptosis, These experimental results demonstrate a distinct function of FDC and activated T cells, in t hat FDC provide signals for rapid proliferation of centroblasts, whereas T cells confer signals for differentiation of centroblasts into centrocytes a nd resistance to B cell receptor-mediated apoptosis, T cells collaborate wi th FDC in the protection and expansion of the Ag-specific GC B cells.